Inhibitory Effect of Tetrandrine on Pulmonary Metastases in CT26 Colorectal Adenocarcinoma–Bearing BALB/c Mice

Abstract

Tumor metastasis is a major cause of mortality in cancer patients. The anti-metastatic effect of tetrandrine, an alkaloid isolated from Stephania tetrandrae S. Moore, was investigated in a pulmonary metastatic model of colorectal cancer-bearing mice. Tetrandrine decreased the viability of murine colorectal adenocarcinoma CT26 cells in a time- and dose-dependent manner. CT26 cells were injected into BALB/c mice via a tail vein to establish pulmonary metastases. After this, the mice were given intraperitoneal injections of tetrandrine (10 mg/kg/day), 5-fluorouracil (5-FU) at the same dose, or vehicle for 5 consecutive days. Mice treated with tetrandrine had 40.3% fewer metastases than vehicle-treated mice, and those treated with 5-FU had 36.9% fewer metastases than controls. Both tetrandrine- and 5-FU-treated mice survived longer than mice in the untreated control group. There was no acute toxicity or obvious changes in body weight in any of the mice. These results suggest that tetrandrine may be a useful anti-metastatic agent.

Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells

“…metastases, compared with vehicle-treated mice, and no acute toxicity or marked changes in body weight were observed (25). The results of the present study indicated that the EGF-induced invasion of HT29 cells was suppressed by tetrandrine through the inactivation of EGFR and downstream molecules, including suppression of the phosphorylation cascade of PI3K, PDK1 and AKT, and the reduction of p-ERK, which was in agreement with a previous study on lung cancer cells (44).…”

“…It has been shown that tumor cell apoptosis caused by tetrandrine exhibits inhibitory effects on various types of tumor cell (24)(25)(26)(27)(28)(29). The results of the present study indicated that tetrandrine had no cytotoxic effect on the HT29 cells, however, the anti-metastatic effect of tetrandrine on EGF-induced HT29 cancer cells was observed, and the underlying molecular signaling was evaluated.…”

“…The dysregulation of human EGFR pathways by the overexpression or constitutive activation promote s tumor processes, angiogenesis and metastasis in several types of human cancer (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Previous studies have demonstrated that tetrandrine inhibits cell metastasis in 4T1 breast cancer cells (18) and CT26 colorectal cancer cells in vivo (25). In the latter, tetrandrine-treated BALB/c mice were found to exhibit fewer Figure 5.…”

“…Tetrandrine has been shown to have broad pharmacological actions (20)(21)(22). Several reports have indicated that tetrandrine presents potent anticancer effects on multiple cancer cells in vitro (23)(24)(25)(26)(27)(28)(29). Tetrandrine retards Wnt/β-catenin signaling and inhibits tumor growth of HCT116 human colorectal cancer (24).…”

Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats

“…12 Another report demonstrated that intraperitoneal injection of 10 mg/kg/day tetrandrine for 5 days (starting from the day of intravenous injection of tumor cells) reduced the number of pulmonary metastatic foci of colon cancers by 40%. 35 However, tumor model used in the colon cancer study represents small tumor model because tumors were treated immediately after injection of tumor cells. In our study, we increased the dose of tetrandrine to 150 mg/kg/day and started treatment either immediately or 5 days after tumor cell inoculation.…”